Venous smooth muscle undergoes changes in function, structure and in its biochemical composition, when obtained from animals and man with experimental and human hypertension. These changes: 1) precede the increased arterial resistance and cardiac output of hypertension; 2) are independent of the increased arterial pressure; and, 3) may reflect similar changes which occur on the arterial side of the circulation, but are then subsequently modified and obscured by the elevated intravascular pressure. Decreased venous compliance and enhanced venous tone also initiates the increased cardiac output of dogs with two kidney, one clip Goldblatt hypertension (2-KGH). Thus, veins may serve as model for vascular derangements in hypertension, as well as participating in the pathogenesis of 2-KGH in dogs. This proposal evaluates the mechanism of venous smooth muscle dysfunction in dogs with 2-KGH, and the relationship of the venous changes to the pathogenesis, maintenance and reversal of the hypertension. The basic vascular alterations, and those resulting from the elevated pressure, will be ascertained by comparison of venous and arterial vascular function and structure, within specific vascular beds. The studies to be performed include: 1) hemodynamic responses of the conscious dog with 2-KGH, and sham controls to vasoactive agents during the development and reversal of the hypertension; 2) functional and structural properties of the vasculature in situ and in vitro; 3) measurement of venous and arterial smooth muscle hexosaminews, protein, and electrolytes essential for vascular reactivity, contractility and extensibility. These experiments will be performed in dogs with 2-KGH, devoid of sympathetic nerve function, and treated with Step I, Step II and Step III antihypertensive drugs. These experiments will definitively evaluate whether vascular dysfunction and hypertrophy are the cause or result of the elevated resistance of hypertension, and the role of the aforementioned systems in the hypertensive process.